This invention relates to biomolecular arrays and, particularly, to methods and apparatus for depositing biological materials in a pattern of array features on a surface of a solid support.
Arrays of binding agents have become an increasingly important tool in the biotechnology industry and related fields. Such arrays, in which such binding agents as oligonucleotides or peptides are deposited onto a solid support surface in the form of an array or pattern, can be useful in a variety of applications, including gene expression analysis, drug screening, nucleic acid sequencing, mutation analysis, and the like.
Such arrays may be prepared in any of a variety of different ways. For example, DNA arrays may be prepared manually by spotting DNA onto the surface of a substrate with a micro pipette. See, Khrapko et al. (1991), DNA Sequence 1:375–388. Or, a dot-blot approach or a slot-blot approach may be employed in which a vacuum manifold transfers aqueous DNA samples from a plurality of wells to a substrate surface. Or, an array of pins can be dipped into an array of fluid samples and then contacted with the substrate surface to produce the array of sample materials. Or, an array of capillaries can be used to produce biopolymeric arrays, as described for example in International Patent Publication WO 95/35505.
In an alternative approach, arrays of biopolymeric agents are constructed in discrete regions on the surface of the substrate. See, e.g., U.S. Pat. No. 5,143,854; and Fodor, et al. (1991), Science 251:767–773.
There is a continued interest in developing methods and devices for making arrays of biomolecules, in which the apparatus is less complicated and more automated and the methods reduce waste of biological material that may be in limited supply, and which result in efficient and reproducible rapid production of more versatile and reliable arrays.
Arrays of biomolecular materials, and methods for their fabrication, are described for example in U.S. Pat. Nos. 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934; 5,472,672; 5,527,681; 5,529,756; 5,545,531; 5,554,501; 5,556,752; 5,561,071; 5,599,695; 5,624,711; 5,639,603; and 5,658,734; in International Patent Publications WO 93/17126; WO 95/11995; and WO 95/35505; and in European Patent Publications EP 742 287; and EP 799 897.
Other publications of interest include: Lockhart, et al. (1996), Nature Biotechnology 14: 1675–1680; Schena, et al. (1995), Science 270: 467–470; Schena, et al. (1996), Proc. Nat'l. Acad. Sci. USA 93:10614–10619; Shalon, et al. (1996), Genome Res. 6: 639–645; Milosavljevic, et al. (1996), Genome Res. 6:132–141; Nguyen, et al. (1995), Genomics 29: 207–216; Piétu, et al. (1996), Genome Res. 6: 492–503; Zhao, et al. (1995), Gene 166:207–213; Chalifour, et al. (1994), Anal. Biochem. 216:299–304; Heller, et al. (1997), Proc. Nat'l Acad. Sci. USA 94: 2150–2155; Lehrach, et al. (1990), Hybridization Fingerprinting in Genome Mapping and Sequencing, Genome Analysis, Vol. 1 (Davies & Tilgham, eds.) (Cold Spring Harbor Press) pp. 39–81; and Schema (1996), BioAssays 18: 427–431.
The use of inkjet printing devices to dispense biochemical agents such as proteins and nucleic acids is suggested or disclosed in, for example, U.S. Pat. Nos. 5,658,802; 5,338,688; 5,700,637; 5,474,796; 4,877,745; and 5,449,754.